The histone deacetylase class I, II inhibitor trichostatin A delays peripheral neurodegeneration
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Peripheral nerves, which consist of an axon and a unique glial cell called a Schwann cell, transduce signals from the brain and spinal cord to target organs. Peripheral nerve degeneration leads to distal motor or sensory disorders such as diabetic neuropathy, Charcot–Marie–Tooth disease, and Gullain–Barré syndrome, with symptoms such as dysesthesia, speech impairment, vision change, erectile dysfunction, and urinary incontinence. Schwann cells play an important role in peripheral nerve degeneration. Therefore, revealing the characteristics of Schwann cells will be essential in understanding peripheral neurodegeneration-related diseases for which there is currently no effective treatment. Trichostatin A (TSA) is a noncompetitive, reversible inhibitor of class I and II histone deacetylases (HDACs). HDACs have been shown not only to deacetylate histones but also to target non-histone proteins involved in diverse signaling pathways. Recent studies have revealed that diverse HDAC subtypes regulate peripheral neurodegeneration. Thus, regulating HDAC levels could be an effective strategy for the development of drugs targeting peripheral nerve-related diseases. In fact, the use of TSA has been investigated for the treatment of many diseases, including degenerative diseases of the central nervous system; however, the effects of TSA on peripheral neurodegeneration have not yet been well established. In this study, we revealed the effect of TSA on the process of peripheral neurodegeneration. TSA successfully inhibited myelin fragmentation, axonal degradation, and trans-dedifferentiation and proliferation of Schwann cells, which are essential phenotypes in peripheral neurodegeneration. Therefore, TSA could be a potential drug for patients suffering from peripheral neurodegeneration-related diseases.
KeywordsTrichostatin A Histone deacetylases Acetylation Schwann cells Demyelination Axonal degradation
We thank Ms. Hyun Woo Jo (Department of Anatomy and Neurobiology, Kyung Hee University, Seoul, Korea) for her valuable discussion. This work was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (Grant No. 2018R1D1A1B07040282) and a grant from Kyung Hee University in 2018 (Grant No. KHU-20181065).
MK, CP, JJ and SGY designed this study and interpreted experimental results. MK, JJ and SGY defined intellectual contents. MK, CP, JJ and SGY performed experiments. MK, JJ and SGY wrote the manuscript. JJ obtained funds from government and Kyung Hee University. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors reported no potential conflict of interests.
All procedures of the current experiment were approved by the Kyung Hee University Committee on Animal Research [KHUASP(SE)-16-043-1].
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